Body fluid balance depends on the gain and loss of water and sodium. Renal mechanisms can slow the rate of water and sodium loss from the body, but ingestion of water and sodium through the mechanisms of thirst and salt appetite is necessary for an ultimate restoration of homeostasis. The maintenance of extracellular volume requires that the central nervous system receives and processes information about the status of body water and sodium. Areas of the forebrain and hindbrain integrate this information in ways that are, on balance, either stimulatory or inhibitory to this ingestive behavior. Several types of vascular sensors and humoral agents normally provide this afferent input. However, under severe environmental challenge or in pathological states, the input and processing of information from sensory systems may be distorted and disrupted. Presently, there is only limited understanding about the nature of interactions of these sensory systems and about how the brain processes this information that is critical for maintaining fluid homeostasis and cardiovascular fitness. The present proposal builds upon the applicant's prior investigations of fluid-related afferent signaling and central processing. The proposed research will employ physiological, pharmacological, and neuroanatomical techniques in the rat that permit the investigation of interactive hormonal (angiotensin, atrial natriuretic peptide), neuropeptidergic (oxytocin, tachykinins) and neural (blood pressure/volume) afferent signals that control hypovolemic thirst and salt appetite. These experiments will generate important new information about basic physiological mechanisms that maintain and restore body fluid homeostasis. An increased understanding of these neurobiological processes will contribute to the well-being of normal individuals exposed to physiological (exercise) and environmental (heat) challenges and of certain types of patients with pathological conditions related to fluid balance (hypertension; congestive heart failure).